Clinical Variants of Primary Sclerosing Cholangitis: When Does Liver Biopsy Make the Diagnosis?

Primary sclerosing cholangitis (PSC) is a cholestatic disorder of unknown aetiology, characterized by inflammation and obliterative fibrosis involving the intrahepatic, extrahepatic bile ducts or both (1). It predominates among men and is frequently associated with inflammatory bowel diseases, particularly with ulcerative cholitis. Although there are animal models of PSC, pathogenesis is still poorly characterized (2). The target of the immune reaction is the medium and large bile ducts. Sensitized bile ducts are damaged by different immune cells that are activated in the gastro-intestinal tract and lymph nodes. Cholangiocytes become activated to express adhesion molecules, inflammatory and profibrogenic cytokines, together growth factors that stimulate the production of fibrous tissue. The diagnosis of PSC is based in patients who present with an alteration of cholestatic enzymes on the basis of magnetic resonance (MRN) cholangiography or direct cholangiography (ERCP) which show the typical changes of the biliary tree with multifocal strictures and segmental dilatation (3). PSC, however, is a heterogeneous disease characterized by at least four variants: 1. “Classical” PSC (involving the intrahepatic, extrahepatic biliary tree or both) 2. Small-duct PSC 3. PSC/autoimmune hepatitis (AIH) overlap syndrome 4. IgG4 associated cholangitis (IAC)